Elucidation of pathogenesis of influenza-related encephalopathy using functional failure in rat glia cells

中枢神经系统(CNS)是血脑屏障(BBB)的免疫特免区。据报道，小胶质细胞和星形胶质细胞等神经胶质细胞在正常和多种疾病状态下的中枢神经系统内产生细胞因子。最近的研究表明，TNFa在各种损伤(感染、缺血、创伤)后的脑损伤中起重要作用。本研究通过脑内注射脂多糖建立了中枢神经系统细胞因子风暴的实验体系，并研究了中枢神经系统促炎性细胞因子对脑和全身的影响。大鼠脊髓内注射脂多糖(30μg，30 0μg)1h后，用核糖核酸酶保护试验检测脑组织IL-1β、IL-6、肿瘤坏死因子α的表达，给药后2 h，脑脊液中IL-1β、IL-6、肿瘤坏死因子α浓度升高。组织学检查证实大鼠脑组织中核因子κB活化，脑组织细胞凋亡，大鼠脑内血管漏出FITC-葡聚糖(Mw，000)所致的血脑损伤。大剂量脑脊液注射后，大鼠血清中IL-6、α浓度明显升高。综上所述，脑内注射脂多糖可激活中枢神经系统免疫系统，产生促炎细胞因子IL-1β、IL-6、肿瘤坏死因子α。此外，中枢神经系统中的肿瘤坏死因子α介导脑细胞凋亡，导致血脑屏障破坏。最后，外周血中细胞因子浓度升高，细胞因子通过血脑屏障漏出。

The central nervous system (CNS) is an immune-privileged site by blood brain barrier (BBB). It is reported that glial cells such as microglia and astrocyte product cytokine in he CNS in normal and several disease states. Recent studies indicated that TNFa plays an important role in brain injury after various kind of insult (infection, ischemia, trauma). In this study, we established the experimental system of cytokine storm in the CNS by intracerabrospinal administration of lipopolysaccharide (LPS) and examined the effect of the proinflammatory cytokines in the CNS for brain and systemic. One hour after intracerabrospinal administration with LPS (30μg, 300μg), expression of IL-1^β, IL-6, TNFα mRNA was detected in rat brain by Rnase Protection Assay(RPA) and two hours after administration, cerebrospinal fluid(CSF) concentration of IL-1β, IL-6, TNFα increased. Histological examination proved activation of NFκB, apoptosis in rat brain, the description of blood brain barieer(BBB) by leak of FITC-Dextran(MW 10,000) from vessel in rat brain Serum concentration of IL-6, TNFα was increased by intracerebrospinal administration with high dose LPS. In conclusion, intracerebrospinal administration with LPS mediated activation of CNS immunosystem and production proinflammatory cytokine, such as IL-1β, IL-6, TNFα. Moreover, TNFα in the CNS mediated brain apoptosis and lead to BBB destruction. Finally peripheral cytokine concentration increased LPS and cytokine leaked through BBB.